PMID- 25727954
OWN - NLM
STAT- MEDLINE
DCOM- 20160229
LR  - 20221207
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 127
IP  - 2
DP  - 2015 Feb
TI  - Target-mediated pharmacokinetic/pharmacodynamic model based meta-analysis and 
      dosing regimen optimization of a long-acting release formulation of exenatide in 
      patients with type 2 diabetes mellitus.
PG  - 170-80
LID - S1347-8613(14)00025-5 [pii]
LID - 10.1016/j.jphs.2014.12.004 [doi]
AB  - A hybrid pharmacokinetic/pharmacodynamic (PK/PD) model with extended-release (ER) 
      process and target mediated drug disposition (TMDD) was developed for exenatide 
      ER to account for its complex absorption process and glucagon-like peptide 1 
      receptor (GLP-1R)-mediated non-linear PK behaviors along with its influences to 
      fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Using hybrid PK/PD 
      model, simulations were done to explore the potential dosing regimens which could 
      achieve likelihood of more pharmacodynamic exposure with respect to FPG and HbA1c 
      over a much shorter period compared with the currently used treatment protocol. 
      The mean PK/PD data about exenatide ER for type 2 diabetes mellitus (T2DM) were 
      digitized from the publications, and the hybrid PK/PD model was performed using 
      the Monolix 4.3 program. The plasma concentration-time and FPG/HbA1c-time 
      profiles for exenatide ER subcutaneously administrated to patients with T2DM were 
      well described by this hybrid model. Monte Carlo simulation was applied to mimic 
      the PK profiles when higher loading dose 7.5 and 5.0 mg exenatide ER were 
      subcutaneously administrated with different dosing intervals at the first 3 weeks 
      of 30-week treatment. Two potentially optimizing schedules could improve the 
      likelihood of achieving much more FPG and HbA1c exposures than currently used 
      clinical treatment protocol.
CI  - Copyright (c) 2014 Japanese Pharmacological Society. Production and hosting by 
      Elsevier B.V. All rights reserved.
FAU - Li, Hanqing
AU  - Li H
AD  - State Clinical Trial Institution of New Drugs, International Mongolian Hospital 
      of Inner Mongolia, No.83, Da Xue East Road, Sai Han District, Hohhot 010065, 
      China. Electronic address: hqltcm@163.com.
FAU - Xu, Jiayin
AU  - Xu J
AD  - Mongolian Pharmaceutical Preparation Center, International Mongolian Hospital of 
      Inner Mongolia, Hohhot 010065, China.
FAU - Fan, Xiaohong
AU  - Fan X
AD  - State Clinical Trial Institution of New Drugs, International Mongolian Hospital 
      of Inner Mongolia, No.83, Da Xue East Road, Sai Han District, Hohhot 010065, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20141211
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Blood Glucose)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
MH  - Blood Glucose
MH  - Delayed-Action Preparations
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Exenatide
MH  - Fasting
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/*pharmacokinetics
MH  - Injections, Subcutaneous
MH  - *Meta-Analysis as Topic
MH  - Models, Biological
MH  - Monte Carlo Method
MH  - Peptides/*administration & dosage/*pharmacokinetics
MH  - Venoms/*administration & dosage/*pharmacokinetics
OTO - NOTNLM
OT  - Dosing regimens
OT  - Exenatide extended-release
OT  - Model based meta-analysis
OT  - Pharmacodynamics
OT  - Pharmacokinetics
EDAT- 2015/03/03 06:00
MHDA- 2016/03/02 06:00
CRDT- 2015/03/03 06:00
PHST- 2014/09/24 00:00 [received]
PHST- 2014/11/30 00:00 [revised]
PHST- 2014/12/02 00:00 [accepted]
PHST- 2015/03/03 06:00 [entrez]
PHST- 2015/03/03 06:00 [pubmed]
PHST- 2016/03/02 06:00 [medline]
AID - S1347-8613(14)00025-5 [pii]
AID - 10.1016/j.jphs.2014.12.004 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2015 Feb;127(2):170-80. doi: 10.1016/j.jphs.2014.12.004. Epub 
      2014 Dec 11.